In controlled experiments normal and immunologically deficient CBA mice were inoculated in footpads, intraperitoneally, or intravenously with whole fresh, fresh supernatant, and fresh filtered supernatant (0.2 mu) or with each of these homogenates after autoclaving or their further exposure to 60Co irradiation (2.5 MR). As controls, mice were inoculated with identically prepared fresh nonsarcoid homogenates by these same routes. Epithelioid- and giant-cell granulomas were present in viscera of mice given each fresh sarcoid homogenate by any of these routes 15 months after inoculation, but were not present in mice given nonsarcoid autoclaved sarcoid, or 60Co-irradiated sarcoid homogenate. Successful passages were achieved following the inoculation of whole or filtered supernatant (0.2 mu) sarcoid mouse tissue homogenate into footpads, intraperitoneally, or intravenously. The epithelioid- and giant-cell granulomas evolved slowly over a period of many months following the inoculation of sarcoid tissue or passage homogenates and persisted thereafter in association with Kveim reactivity. The transmissible agent is inactivated when homogenate prepared from human sarcoid or mouse sarcoid tissue is autoclaved or 60Co-irradiated, can be repeatedly passaged, and has been shown to pass an 0.2-mu membrane filter. It is therefore presumably viable and must approximate to the size of a virus or be capable of being deformed so as to pass a filter of such a pore size (0.2mu), L forms.